Antidepressant agomelatine attenuates behavioral deficits and concomitant pathology observed in streptozotocin-induced model of Alzheimer's disease in male rats.

Abstract Experimental findings suggest that the melatonin system has a beneficial role in models of Alzheimer's disease (ADs). The aim of the present study was to explore whether the atypical antidepressant agomelatine (Ago), which is a melatonin MT 1 and MT 2 agonist and 5-HT 2C antagonist, is effective against behavioral, biochemical and histological impairments in streptozotocin (STZ)-induced model of ADs in male rats. Male Sprague Dawley rats were treated intraperitoneally (i.p.) with Ago (40 mg/kg) for 30 days starting three months following the intracerebroventricular (icv) injection of STZ. Chronic Ago treatment reduced anxiety-like behavior of STZ-treated rats in the elevated plus maze, increased the preference to saccharine and corrected the spatial memory impairment in the eight-arm radial arm maze test. This melatonin analogue restored STZ-induced biochemical changes, including an increase of beta amyloid (Aβ) protein, and signal markers of inflammation (TNF-alpha and IL-1 beta). Ago exerted partial neuroprotection, specifically in the temporal CA3b subfield of the dorsal hippocampus and temporal piriform cortex. The ability of Ago to alleviate behavioral symptoms and concomitant neuropathological events observed in a model of sporadic ADs suggests that this melatonin alternative can be considered a promising adjuvant in this disease. Highlights • Agomelatine treatment attenuated behavioral changes in icv STZ rats. • Agomelatine reduced Aβ 42 accumulation in the FC and hippocampus. • Agomelatine alleviated pro-inflammatory signal molecules. • Agomelatine exerted partial neuroprotection in the CA3b subfield and piriform cortex. [ABSTRACT FROM AUTHOR]